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3 Background Direct Mechanical Ventricular Actuation (DMVA) is a unique, non-blood contacting, biventricular assist device that is being developed for support of the failing heart (Myotech Circulatory Support System (CSS)). The device is contoured to fit over the heart and attaches to the ventricular myocardium by an atraumatic vacuum seal (Figure 1). A pneumatic drive is then used to deliver positive (systolic) and negative (diastolic) actuating forces to the ventricular surface. DMVA has been shown to be effective in both laboratory and clinical applications for supporting the fibrillating, asystolic or severely failing heart. Current research is focused on utilizing a rabbit model of heart failure. Figure 1. Schematic of DMVA actuating the failing heart

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12 Summary and Conclusions A rabbit model of acute heart failure has been successfully developed for assessing DMVA. The primary focus of these experiments is to determine how DMVA affects myocardial wall stress and maladaptive cell signaling characteristic of the failing heart. Current results indicate that DMVA can significantly augment the failing heart while reducing myocardial stress. These findings suggest that DMVA can provide adequate hemodynamic support while favorably altering the maladaptive pathophysiology of heart failure.

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13 Future Studies Ongoing studies are further evaluating DMVA’s impact on maladaptive cellular responses which characterize HF including anti- and pro-apoptotic cell signaling, plasma membrane disruptions and collagen turnover. Mitochondrial function and detailed analysis of regional myocardial wall motion are also under investigation. Findings are expected to determine if and how DMVA favorably alters pathologic remolding of the failing heart.